Published European Patent Application No. 154,142, and U.S. application Ser. No. 755,863, now abandoned, filed July 17, 1985 which are incorporated herein by reference, which was refiled as Ser. No. 885,511, now U.S. Pat. No. 4,690,928 disclose the compound (2R,12bS)-N-(1,3,4,6,7,12-hexahydro-2H-benzo[b]furo[2,3-a]quinolizin-2-yl) -N-methyl-2-hydroxyethanesulfonamide and the enantiomeric quinolizin-2-one intermediate and alternate routes for their syntheses. With the present invention there is provided a new enantioselective route for the synthesis of the intermediate.
The quinolizin-2-one intermediate was previously prepared by standard chemical resolution of racemic ketoamine with L-(+)di-p-toluoyl tartaric acid to give (-)12b(S)-ketoamine in 30-35% yield. A resolution process has a maximum yield of 50%, thus one must always lose 50-65% of the total racemic material being resolved. The present invention produces 12b(S)-ketoamine of greater than 90% optical purity, with optimization to 99% optical purity possible. This invention obviates the need for chemical resolution and, thus, provides a more efficient synthesis of the (-)-12b(S)-ketoamine.